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We accept that life is
finite and ageing inevitable.
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But we explore all options
to battle the diseases that
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come with ageing.
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If we want to be able
to postpone, or even
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prevent age related
disease, we need
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to understand what
changes in an ageing body.
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Ageing is, however, an
incredibly complex phenomenon.
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Why can pine trees live
thousands of years,
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while a mayfly lives minutes?
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Or within species,
why do some people
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live to become 123, while
most live till their 80s?
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Humans are built of trillions
of cells of different types.
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In some complex way, the
health state of all these cells
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is equal to the health state
of a person as a whole.
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To understand the
age-related changes
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in cells on a
molecular level, it
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makes sense to use a model
organism, like the yeast.
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Baker's yeast is a
unicellular organism,
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meaning one cell is
the whole organisms.
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Many genes that extend
lifespan in yeast
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also do so in worms,
flies, and mice.
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So yeast ageing
measured in one cell
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is a model for ageing organisms
much larger than yeast.
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What does the life of a
yeast cells look like?
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A yeast cell produces a new cell
approximately every two hours.
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A harmless scar is left
behind on the mother,
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but changes inside
the mother have
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begun to take place that
are not yet fully understood
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and contribute to its ageing.
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A mother cell that has produced
10 daughters has 10 scars.
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And we say her
replicative age is 10.
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After the cell has produced
between some 20 to 30 daughter
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cells, it dies.
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The daughter cells have
youthful characteristics.
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This must mean that the daughter
cell did not inherit whatever
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it is that killed her mother.
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Looking inside a cell, you'll
see a world of its own.
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Biologists have described
it to a great extent.
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This resembles a little factory.
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It is a ribosome that
is making a protein.
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This resembles a power plant.
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It is a mitochondrion
making energy.
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This resembles a library.
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It is the nucleus that keeps the
chromosomes, the book of life.
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Molecular copy machines
can copy the DNA.
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All parts of this molecular
world inside the cell
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communicate and work together,
for which there are means
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of communication and transport.
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This is, for example, a motor
protein that carries a vesicle.
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If everything in this
small, one-celled world
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works well, and provided
conditions are right,
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the cell will produce an
extra copy of everything
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inside the cell so that when
some two to three hours later,
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when a new cell is
born, it is equipped
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with everything required.
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So how is an old yeast cell
different from a young yeast
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cell?
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When we compare them, we
see that the molecular world
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in an old cell is
indeed different.
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For making a daughter
cell, it would be perfect
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if double the amount of
everything inside the cell
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was made.
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But instead, the mother
cell makes a bit too much
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of some parts, and
too little of others.
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Also some parts wear down
more easily than others.
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This is a problem if components
have to work together
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to be functional.
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Dysfunctional and potentially
harmful molecular machines
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appear.
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Brave mother tries
her best to keep
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all these damaged molecular
machines to herself,
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and to equip the daughter
cell with a perfect set
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of molecular machines.
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This now was the example of how
ribosome function main impact
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ageing.
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But the big question
for the coming years
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is to dissect cause
and consequence.
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So just to name
some, are mistakes
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on the DNA, the book
of life, a first cause,
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or are they a consequence
of malfunctioning
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molecular machines
for copying that DNA?
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Could it be that these molecular
copying machines are not
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doing their jobs well
because the ribosomes,
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the little factories, produce
them in a dysfunctional state?
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Finding these, and many other
putatively causal relationships
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will be critical to
understanding cellular ageing.
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We believe the strategy to work
with a well controlled model
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system pays back when
dealing with complex issues
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like ageing.
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